This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this project is to determine the structural basis of glucose transporters (GLUTs or SLC2) function. GLUTs are transmembrane proteins that transport carbohydrates (glucose, fructose and others), major energy sources for living cells, across cell membranes. Fourteen human GLUTs indentified so far share similar sequences, but have different substrate specificity and tissue distribution. The activity or/and localization of GLUT2, 4 and 5 are affected in diabetes. Ligands of GLUTs are used in diagnostic imaging of cancers and are emerging as new alternatives in the treatment of human cancers. Despite the overriding importance of GLUTs, there is no three dimensional structure information available for any of the human glucose transporters or for their homologues. Determining the 3D structure of any GLUT will be a remarkable breakthrough in the study of this fundamental transport system and will open new research avenues.